Neurobiological Adaptations to Psychostimulants and Opiates as a Basis of Treatment Development

Abstract

Abuse of illicit substances, in particular psychostimulants and opiates, is a worldwide public health issue. Chronic use of cocaine and amphetamine causes common neurobiological adaptations that may guide new treatment development. These include perturbations in dopamine and serotonin neurotransmission, leading to trials of antidepressants, and serotonin and dopamine augmentation strategies. The detection of cerebral perfusion abnormalities caused by psychostimulants has led to examination of antiplatelet and excitatory amino acid (EAA) antagonist therapies. Further, development of cocaine vaccines allows for testing of peripheral blockade approaches to cocaine addiction. New approaches to behavioral treatments for cocaine dependence are also reviewed. For opiate dependence, understanding of heroin's effects on μ and κ opiate receptors has led to investigations of the partial μ agonist buprenorphine in opiate maintenance. Evidence for hyper‐excitability of locus coeruleus (LC) noradrenergic neurons and EEA inputs to the LC guides trials of new α2‐adrenergic agonists and EEA antagonists to alleviate opiate withdrawal. Finally, clinical experience with withdrawal from methadone and LAAM has led to trials of antagonist‐accelerated opiate withdrawal. Improved treatment of psychostimulant and opiate addiction is critically needed, and likely to have wide‐reaching impact in health care and society.

Markers in Morphine- and Cocaine-Addicted Animals

“…Opiates and psychostimulants produce addictions after repeated administrations in animals and human (Heyne and Wolffgramm, 1998;Sevarino et al, 2000).…”

“…Opiates and psychostimulants produce addictions after repeated administrations in animals and human (Heyne and Wolffgramm, 1998;Sevarino et al, 2000).Opiates such as heroin and morphine remain widely abused drugs with a high physical dependence liability (Pouletty, 2002). Opiates, acting on opioid receptors via Gi/Go classes of the G proteins, inhibit cyclic AMP (cAMP) formation (ColThese experiments were designed to use typical makers from behaviors and molecular basis in addicted animals of morphine and cocaine.…”

Vaccines against morphine/heroine and its use as effective medication for preventing relapse to opiate addictive behaviors

“…1,7 The risk of relapse currently precipitated by drug-associated Vaccines against morphine/heroin and its use as effective medication for preventing relapse to opiate addictive behaviors to maintain and restore the pre-existing functional homeostasis of implicated neural circuits and their operant neurons altered during opiate abuse, prior to the compulsive drug-intake behavior. 24 Once these neuroadaptations have been established, the abrupt suspension of the drug-intake behavior enhances the development of new series of neurobiological changes and cellular adaptations in the neurons impinged by the drug, leading to the neuropathological basis that underlies the withdrawal syndrome during drug addiction. The withdrawal syndrome produced by both morphine and heroin in the addicted individual, as opposed to the withdrawal syndrome induced by cocaine and amphetamine, is characterized by highly intense physical and psychological alterations in affected subjects.…”

“…The withdrawal syndrome produced by both morphine and heroin in the addicted individual, as opposed to the withdrawal syndrome induced by cocaine and amphetamine, is characterized by highly intense physical and psychological alterations in affected subjects. [24][25][26] Epidemiology and risk factors of opiate dependence. The illicit opiate use has extended worldwide and existed in Western countries (Europe and North America) for over a century.…”

“…For instance, the repetitive administration of heroin by an addict, produces an increase stereotyped compulsive behaviors leading to uncontrolled drug-intake behavior, associated with stereotyped rites of administration, initially accompanied by pharmacological tolerance and subsequently by physical signs and symptoms of drug withdrawal after acute suppression of the opiate drug. 24 Thus, heroin-intake behavior becomes the highest priority and necessity in the addicted individual, leading to the reinstatement of compulsive drug-intake and drug-seeking behaviors normally observed during drug withdrawal or abstinence. The neuroadaptative changes occurring during opiate addiction is primarily caused by the pharmacological actions displayed by the repetitive exposure of the drug over a clustered group of neurons localized in different areas of the brain.…”